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. 2025 Nov 25;25(1):1914.
doi: 10.1186/s12885-025-15298-z.

Real-world insights into the prevalence and prognostic significance of trophoblast cell-surface antigen 2 and folate receptor alpha in uterine carcinosarcoma

Lucas Zanetti de Albuquerque #  1 , Jessé Lopes da Silva #  1 , Fabiana Resende Rodrigues  2 , Priscila Valverde Fernandes  2 , Isabele Ávila Small  1 , Luís Felipe Leite  1 , Gustavo Guitmann  3 , Andreia Cristina de Melo  4
Affiliations

Real-world insights into the prevalence and prognostic significance of trophoblast cell-surface antigen 2 and folate receptor alpha in uterine carcinosarcoma

Lucas Zanetti de Albuquerque et al. BMC Cancer. .

Abstract

Background: Uterine carcinosarcomas (UCS) are rare and aggressive gynecological tumors and the description of biomarkers that can help guide targeted treatments in this disease is a critical gap in current medical research. This study aims to measure the prevalence of trophoblast cell-surface antigen 2 (Trop-2) and folate receptor alpha (FRα) in UCS and evaluate their prognostic significance.

Methods: This retrospective analysis examined data from female patients diagnosed with UCS who underwent surgery followed by carboplatin and paclitaxel chemotherapy between January 2012 and December 2020. Tissue microarrays from 89 samples were assessed for Trop-2 and FRα expression by IHC. High positivity was defined as a score of ≥ 50% of tumor cells with strong staining intensity for Trop-2 and ≥ 75% with medium or strong staining intensity for FRα. Sociodemographic and clinical features were analyzed alongside progression-free survival (PFS) and overall survival (OS) outcomes.

Results: The mean age at diagnosis was 66.2 years (Standard Deviation, SD: 7) and the mean body mass index was 28.7 kg/m² (SD: 6.2). Non-white women accounted for 71.6% of cases. Heterologous subtype corresponded to 63.0% of cases, and lymphovascular invasion was observed in 59.2%. Complete resection (R0) was achieved in 66.3% of cases. High expression of Trop-2 and FRα was found in 49.4% and 17.4% of epithelial components, respectively, with no high positivity in sarcomatous components. Negative margins were more common in stage I/II disease (p = 0.001), and FRα overexpression correlated with Trop-2 overexpression (p = 0.007). On multivariate analysis, advanced stage (p = 0.015) and incomplete resection (p < 0.001) predicted shorter PFS, while both factors also independently worsened OS (p = 0.013 and p = 0.001, respectively). Lymphadenectomy was associated with improved OS (p = 0.025).

Conclusion: Complete resection and advanced stage were suggested as prognostic factors in UCS. FRα and Trop-2 are increasingly recognized as therapeutic targets and their elevated expression levels in the epithelial component of UCS are promising, although not associated with prognosis in this cohort.

Keywords: Biomarkers; Folate receptor alpha; Trophoblast cell-surface antigen 2; Uterine carcinosarcoma.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethics approval was obtained from the Institutional Review Board (Ethics Committee for Human Research of the Brazilian National Cancer Institute), under registration number 03727818.2.0000.5274. The study was conducted in accordance with the Good Clinical Practice (GCP) guidelines established by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). It was also aligned with core principles from the 2000 version of the Declaration of Helsinki, as referenced by Brazilian Resolution No. 466/2012 of the National Health Council, which regulates research involving human subjects in Brazil. Given the retrospective observational design of this study, the committee waived the requirement for obtaining informed consent from all participants. Consent for publication: Not applicable. Competing interests: ACM has received grants or contracts from Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, GSK, MSD, Novartis, Pierre Fabre, Regeneron Pharmaceuticals, and Roche, with payments made to the institution. ACM also reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Adium, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, GSK, MSD, Novartis, and Roche. The other authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Graphic representation of the immunohistochemistry biomarkers staining. IHQ positivity, grading from negative to low, moderate and high expression, is demonstrated for both FRα and Trop-2 on epithelial and sarcomatous components of UCS
Fig. 2
Fig. 2
Immunohistochemistry staining representation of Trop-2 and FRα expression on the epithelial component of UCS. The images were captured at a magnification of x20 to ensure precision
Fig. 3
Fig. 3
Progression-free survival (PFS). PFS by stage (A), lymphadenectomy (B), residual disease status (C) and dichotomized (high versus negative, low and moderate) immunohistochemistry expression levels of FRα (D) and Trop-2 (E) on the epithelial component of UCS. Margin status after surgery was stratified according to the size of residual disease into R0 (without residual disease, inferior to 1.0 cm in size), R1 (microscopic residual disease) and R2 (macroscopic residual disease). As for immunohistochemistry markers, Kaplan Meier curves for PFS were stratified by the cut-off points previously set up and divided into negative, low, moderate versus high positivity expression of both biomarkers. Tick marks indicate censored data
Fig. 4
Fig. 4
Overall survival (OS). OS by stage (A), lymphadenectomy (B), residual disease status (C) and dichotomized (high versus negative, low and moderate) immunohistochemistry expression levels of FRα (D) and Trop-2 (E) on the epithelial component of UCS. Margin status after surgery was stratified according to the size of residual disease into R0 (without residual disease, inferior to 1.0 cm in size), R1 (microscopic residual disease) and R2 (macroscopic residual disease). As for immunohistochemistry markers, Kaplan Meier curves for OS were stratified by the cut-off points previously set up and divided into negative, low, moderate versus high positivity expression of both biomarkers. Tick marks indicate censored data
Fig. 5
Fig. 5
Swimmer plot highlighting important timepoints on patients’ follow-up. Swimmer plot depicts disease assessments relevant to curative treatment, recurrence and palliative chemotherapy, highlighting patients with high FRα and/or Trop-2 expression. Each horizontal bar represents an individual patient. The timeline is aligned by the date of surgery, and key clinical milestones are annotated for each case
See this image and copyright information in PMC

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